Detection of Helicobacter pylori strain types and analysis of risk factors among subjects from Hainan Province, China.

OBJECTIVE: To explore the prevalence of type I and type II Helicobacter pylori infection and investigate risk factors in a population from Hainan Province in China. METHODS: Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping. RESULTS: In total, 410 subjects were investigated for H. pylori strain types. The overall prevalence of the highly virulent, type I H. pylori strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I H. pylori infection in smokers compared with non-smokers, and a higher risk of H. pylori type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values. CONCLUSION: Highly virulent, type I H. pylori infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I H. pylori infection. We found that Type I H. pylori was closely associated with peptic ulcer disease and the DOB values were generally high.

Comparison of vonoprazan dual therapy, quadruple therapy and standard quadruple therapy for Helicobacter pylori infection in Hainan: a single-center, open-label, non-inferiority, randomized controlled trial.

OBJECTIVE: To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province. METHODS: A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18-75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT). RESULTS: The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%-95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%-98.4%), 92.7% (38/41, 95%CI 84.4%-101.0%),88.4% (38/43，95%CI 78.4%-98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy. CONCLUSION: VPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.

Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Recurrence Rate and Influencing Factors of Helicobacter Pylori Infection After Successful Eradication in Southern Coastal China.

Purpose: Recurrence rate of Helicobacter pylori (H. pylori) infection after successful eradication have gained attention. This study was to assess the recurrence rate of H. pylori infection after successful eradication in the southern coastal provinces of China and to analyze its factors. Patients and Methods: 975 patients with upper gastrointestinal symptoms who were diagnosed with H. pylori infection using the 13C or 14C-urea breath test (UBT) underwent eradication treatment between August 2021 and December 2022. After eight to twelve weeks, repeat UBT was performed. Besides, 824 patients with successful eradication underwent a repeat UBT by completing questionnaires after a year. The 1-year recurrence rate was calculated, and the differences were analyzed based on baseline data, sociological characteristics, and lifestyle. Results: A total of 734 patients completed the 1-year follow-up, out of which 26 (3.5%) patients experienced a recurrence of H. pylori infection. Exposure to other individuals infected with H. pylori (χ2=12.852, P<0.001), poor hygiene conditions at dining out places (χ2=6.839, P=0.009), frequent dining out (χ2=24.315, P<0.001), smoking (χ2=7.510, P=0.006), consumption of non-purified water (χ2=16.437, P<0.001), consumption of pickled foods (χ2=5.682, P=0.017), irregular meal patterns (χ2=16.877, P<0.001) and age (χ2=9.195, P=0.010) were significant factors for H. pylori infection recurrence. Exposure to other individuals infected with H. pylori, poor hygiene conditions at dining out places, consumption of non-purified water, frequent dining out and irregular meal patterns were independent risk factors (P=0.022, 0.016, 0.002, <0.001, <0.001; 95% CI 0.146-0.861, 0.121-0.806, 1.715-10.845, 0.085-0.521, 2.291-14.556). Conclusion: The one-year recurrence rate of H. pylori infection post-eradication in the southern coastal provinces of China is 3.5%. Contacting with infected individuals, poor hygiene in dining places, consumption of non-purified water, frequent dining out, and irregular meal patterns were identified as significant independent factors influencing H. pylori recurrence.

Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

BACKGROUND: Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. METHODS: In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. RESULTS: Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. CONCLUSIONS: This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

H. pylori infection and osteoporosis: a large-scale observational and mendelian randomization study.

PURPOSE: There is controversy concerning the relationship between Helicobacter pylori (H. pylori) infection and osteoporosis. This study is to examine the causal relationship between H. pylori infection and osteoporosis and to analyze the potential mechanism underlying the relationship. METHODS: The clinical data of H. pylori infection and bone mineral density from patients or physical examiner with good general condition in our hospital between September 2019 and September 2020 were retrospectively collected. The relationship between H. pylori infection and osteoporosis was compared and analyzed, using logistic regression to examine the potential mechanism underlying the association. To investigate the causal effects of H. pylori infection and osteoporosis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis. RESULTS: A total of 470 patients were positive for H. pylori, with a detection rate of 52.22%. It was found that age, SBP, FPG, DBP, ALB, LDL-C, hs-CRP, and OC were positively correlated with osteoporosis, while negative correlations were observed with BMI, LYM, ALB, TP, TG, HDL-C, SCr, UA, and VitD. After stratified analysis of sex and age, it was found that there was a significant correlation between H. pylori infection and osteoporosis. The levels of SBP, ALP, FPG, LDL-C, hs-CRP, and OC in both H. pylori-positive group and osteoporosis group were higher than those in the H. pylori-negative group while the levels of BMI, ALB, TP, HDL-C, SCr, UA, and VitD in the positive group were significantly lower than those in the negative group. Logistic regression analyses with gender and age showed that ALB, FPG, HDL-C, and VitD were common risk factors for osteoporosis and H. pylori infection. In the MR analysis, the IVW results found a positive effect of H. pylori infection on osteoporosis (OR = 1.0017, 95% CI: 1.0002-1.0033, P = 0.0217). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of osteoporosis on H. pylori infection. CONCLUSION: Our study provides evidence for causal effects of H. pylori infection on osteoporosis. H. pylori may affect osteoporosis through serum albumin, high-density lipoprotein, fasting blood glucose and vitamin D.

Prevalence, types, and risk factors of functional gastrointestinal diseases in Hainan Province, China.

To investigate the prevalence, types, and risk factors of functional gastrointestinal diseases (FGIDs) in Hainan Province, China, in order to provide insights for future prevention and treatment strategies. A questionnaire survey was conducted from July 2022 to May 2023, using stratified sampling to sample local residents in five cities (20 townships) in Hainan Province. Out of 2057 local residents surveyed, 659 individuals (32.0%) reported experiencing at least one FGID. The most prevalent FGIDs were functional dyspepsia (FD) (10.7%), functional constipation (FC) (9.3%), irritable bowel syndrome (IBS) (6.8%), functional bloating (2.2%), belching disorder (2.2%), functional diarrhea (FDr) (1.5%), functional heartburn (1.5%), and fecal incontinence (0.98%). The study revealed significant associations between FGIDs and factors such as age, sleep quality, anxiety, smoking, alcohol consumption, and the consumption of pickled food (P < 0.05). Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as independent risk factors for the prevalence of FGIDs (P < 0.05). In Hainan Province, the overall prevalence of FGIDs was found to be 32.0%, with higher prevalences of FC and FD. Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as risk factors for FGIDs.

Removal of a guide-wire sliding into abdominal cavity via transgastric natural orifice transluminal endoscopic surgery: A case report.

BACKGROUND: Guidewire slippage into the peritoneal cavity during clinical operations is extremely rare. Therefore, this paper aims to report a successful case of guidewire removal using transgastric natural orifice transluminal endoscopic surgery (NOTES). The goal is to enhance physicians' understanding of the management plan for this unique scenario and provide a valuable reference for clinical practice. CASE SUMMARY: A 64-year-old man presented with abdominal distension and was diagnosed with cirrhosis combined with massive ascites. To proceed with treatment, the patient underwent ultrasound-guided peritoneal puncture and underwent catheterization and drainage. Unfortunately, a 0.035-inch guidewire slipped into the abdominal cavity during the procedure. Following a comprehensive evaluation and consultation by a multidisciplinary team, the guidewire was successfully removed using NOTES. CONCLUSION: This case highlights the potential consideration of transgastric NOTES removal when encountering a foreign body, such as a guidewire, within the abdominal cavity.

A survey on Helicobacter pylori infection rate in Hainan Province and analysis of related risk factors.

OBJECTIVE: The aim of this study was to understand the prevalence and potential risk factors of Helicobacter pylori (H. pylori) infection in Hainan Province, China. METHODS: We conducted this study in 21 health service stations in 5 cities of Hainan Province from August 2022 to April 2023. We selected the various participants based on a stratified whole-group sampling method. The 14C-UBT was used to analyze H. pylori infection in 3632 participants. We also analyzed the possible relationship between variables and H. pylori infection based on chi-square test and multifactorial logistic regression. The model was evaluated by performing a Hosmer-Lemeshow goodness-of-fit test and plotting receiver operating characteristic(ROC) curves. RESULTS: In total, the results of 3632 eligible participants (age: 14 to 93 years) were included in the analysis. The total prevalence of H. pylori infection in Hainan Province was approximately 38.7%. The prevalence of H. pylori infection was found to increase with age, stabilized in the age group of 45 to 64 years, but peaked in the age group of 65 years and older. In multifactorial analysis, the prevalence of H. pylori infection was positively associated with middle-aged adults (45-64 years), older adults (≥ 65 years), drinking, farmers, natural labor, routinely share utensils, have habit of frequent betel nut consumption, upper gastrointestinal symptoms, and family history of gastric cancer. The factors negatively associated with prevalence included family size ≤ 3, washing hands often before meals, frequent exercise, regular meals, and frequent consumption of fruits and vegetables. In addition, the Hosmer-Lemeshow test showed a good fit (χ2 = 12.983, P = 0.112) and the area under ROC was 0.631 (95%CI: 0.613 ~ 0.649). CONCLUSION: The prevalence of H. pylori infection in Hainan Province was observed to be moderate and closely related to age, local socioeconomic conditions, hygienic status and dietary habits.

Roles of Gut Microbiota in Alcoholic Liver Disease.

Alcoholic liver disease (ALD)-one of the most common liver diseases - involves a wide range of disorders, including asymptomatic hepatic steatosis, alcoholic hepatitis (AH), liver fibrosis, and cirrhosis. Alcohol consumption induces a weakened gut barrier and changes in the composition of the gut microbiota. The presence of CYP2E1 and its elevated levels in the gastrointestinal tract after alcohol exposure lead to elevated levels of ROS and acetaldehyde, inducing inflammation and oxidative damage in the gut. At the same time, the influx of harmful molecules such as the bacterial endotoxin LPS and peptidogly from gut dysbiosis can induce intestinal inflammation and oxidative damage, further compromising the intestinal mucosal barrier. In this process, various oxidative stress-mediated post-translational modifications (PTMs) play an important role in the integrity of the barrier, eg, the presence of acetaldehyde will result in the sustained phosphorylation of several paracellular proteins (occludin and zona occludens-1), which can lead to intestinal leakage. Eventually, persistent oxidative stress, LPS infiltration and hepatocyte damage through the enterohepatic circulation will lead to hepatic stellate cell activation and hepatic fibrosis. In addition, probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), bioengineered bacteria, gut-restricted FXR agonists and others are promising therapeutic approaches that can alter gut microbiota composition to improve ALD. In the future, there will be new challenges to study the interactions between the genetics of individuals with ALD and their gut microbiome, to provide personalized interventions targeting the gut-liver axis, and to develop better techniques to measure microbial communities and metabolites in the body.

Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice.

Carnobacterium maltaromaticum was found to be specifically depleted in female patients with colorectal cancer (CRC). Administration of C. maltaromaticum reduces intestinal tumor formation in two murine CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltaromaticum via increasing the colonic expression of SLC3A2 that binds to DD-CPase of this bacterium. Metabolomic and transcriptomic profiling unveils the increased gut abundance of vitamin D-related metabolites and the mucosal activation of vitamin D receptor (VDR) signaling in C. maltaromaticum-gavaged mice in a gut microbiome- and VDR-dependent manner. In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: a prospective follow-up cohort study.

BACKGROUND: Acute gastrointestinal infections can lead to post-infectious irritable bowel syndrome (PI-IBS). Moreover, coronavirus disease (COVID-19) is related to long-term gastrointestinal sequelae. In this study, the frequency, disease spectrum, and risk factors for post-infection functional gastrointestinal disease (PI-FGID) in COVID-19 patients and healthy controls were prospectively examined. METHODS: Validated Rome III and Rome IV questionnaires and limited objective assessment were used to assess the incidence of PI-FGID in 190 COVID-19 patients, and 160 healthy controls prospectively followed for 1, 3, and 6 months. RESULTS: Six(3.2%), 1(0.5%), 3(1.6%), 5(2.6%), 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at 1 month, respectively, while 4(2.1%), 1(0.5%), 4(2.1%), 4(2.1%), and 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at three months, respectively. Furthermore, 2(1.3%), 4(2.5%), and 3(1.9%)healthy controls developed constipation, dyspepsia, and their overlap at one month, respectively (P = 0.193), while 2(1.3%), 4(2.5%), and 2(1.3%)healthy controls developed constipation, dyspepsia and their overlap at three months, respectively (P = 0.286). FGIDs incidence was higher among COVID-19 patients(8.9%) than in healthy controls(3.1%) at 6-month follow-up (P = 0.025). Moreover, 7 (3.7%), 5 (2.6%), 3 (1.6%), and 2 (1.1%) COVID-19 patients developed IBS, functional dyspepsia(FD), functional diarrhea(FDr), functional constipation(FC)at six months, respectively, while only 2 (1.3%) and 3 (1.9%) healthy controls developed IBS and FD at six months, respectively. Notably, gastrointestinal(GI)symptoms at onset were the independent risk factors for post-COVID-19 FGIDs at six months. CONCLUSIONS: COVID-19 increases new-onset PI-FGID at six months compared with healthy controls. GI symptom at the onset of COVID-19 is an independent risk factor for post-COVID-19 FGIDs.

Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease Among Hospital Staff.

Background: The prevalence of metabolism-related fatty liver disease (MAFLD) has been rarely reported in hospital staffs. The aim of this study was to assess the prevalence and risk factors for MAFLD in hospital staffs aged ≥18 years. Methods: Based on type B ultrasonic, hospital staffs who underwent medical examinations at the second Affiliated Hospital of Hainan Medical University from January 2022 to March 2022 were classified into health control group (661 subjects) and MAFLD group (223 subjects), demographic, biochemical and blood examination information were compared between 2 groups. Independent risk factors for MAFLD were determined by logistic regression. Predictive values of risk factors of MAFLD were evaluated by receiver operating characteristic (ROC) curves. Results: The prevalence of MAFLD was 33.7%. Older age (OR=1.08, p<0.001), H. pylori infection (OR=0.234, p=0.02), triglyceride-glucose (TyG) (OR=7.001, p<0.001), low-density lipoprotein cholesterol (LDL-C) (OR=2.076, p=0.028), red blood cell (RBC) (OR=2.386, p=0.001), eating out (OR=0.048, p=0.001), regular exercise (OR=23.017, p<0.001), and overweight (OR=3.891, p=0.003) were independently associated factors for MAFLD. The AUC of model predicting MAFLD is 0.910 [95% CI (0.886, 0.934)], with 0.794 sensitivity, 0.908 specificity. The diagnostic value of model was higher in the female MAFLD group after stratified analysis according to gender. The model showed that TyG was the factor contributing more to MAFLD. The diagnostic value of TyG was higher in the female MAFLD group than male MAFLD group. Conclusion: The prevalence of MAFLD among hospital staffs was 33.7%. TyG can be used to predict MAFLD especially for female hospital staffs for early intervention.

Esophageal cancer-related gene 4 inhibits gastric cancer growth and metastasis by upregulating Krüppel-like factor 2 expression.

Background: There are a large number of people suffering from gastric cancer (GC) worldwide, so the study of biomarkers for GC is urgently needed. This study aimed to investigate the role of esophageal cancer-related gene 4 (ECRG4) in the growth, metastasis, and prognosis of GC and the possible underlying mechanism. Methods: The expression of ECRG4 was detected in GC tissues by quantitative polymerase chain reaction (PCR), Western blot, and immunohistochemistry. The relationships between ECRG4 expression and clinicopathological parameters of patients with GC were statistically analyzed, and Kaplan-Meier prognosis and survival curves of the patients were plotted. ECRG4 was overexpressed in the human gastric adenocarcinoma cell line (AGS) and human GC cell line 27 (HGC27), and the in vivo effects of ECRG4 overexpression on the growth, invasion, and metastasis of GC were analyzed and verified in nude mice. To identify the downstream transcription factors potentially regulated by ECRG4, ribonucleic acid (RNA) sequencing and differential gene expression analysis were performed on ECRG4-overexpressing cells. Quantitative PCR, Western blot, and immunohistochemistry were used to detect the expression of the downstream transcription factors targeted by ECRG4 in GC. Results: The ECRG4 mRNA and protein expression levels were low in GC tissues and were associated with a poor prognosis. Least absolute shrinkage and selection operator (LASSO) Cox regression and Kaplan-Meier survival analyses showed that patients with low ECRG4 expression had worse prognosis and survival. Overexpression of ECRG4 inhibited the proliferation, metastasis, and invasion of GC cells. RNA sequencing analysis showed that overexpression of ECRG4 induced the upregulation of Krüppel-like factor 2. Conclusions: Our findings show that ECRG4 promotes GC progression via Krüppel-like factor 2 signaling and highlight ECRG4 as a potential GC biomarker and therapeutic target.

CYP2C19 gene polymorphism in Ningxia.

BACKGROUND: Poor metabolizer (PM) status of CYP2C19 can be a predisposing factor for developing gastric cancer in H. pylori-infected patients. It is unclear whether PM status of CYP2C19 can also be a potential factor for H.pylori infection in healthy people. METHODS: We used high-throughput sequencing to detect single nucleotide polymorphisms (SNPs) at just three loci, rs4244285 (CYP2C19*2), rs4986893 (CYP2C19*3) and rs12248560 (CYP2C19*17), to identify the exact CYP2C19 alleles corresponding to the mutated sites. We determined CYP2C19 genotypes of 1050 subjects from 5 cities of Ningxia from September 2019 to September 2020 and evaluated the potential correlation between H.pylori and CYP2C19 gene polymorphisms. Clinical data were analyzed using χ2 tests. RESULTS: The frequency of CYP2C19*17 in Hui (3.7%) was higher as compared to Han (1.4%) in Ningxia (p = 0.001). The frequency of CYP2C19*1/*17 of Hui (4.7%) was higher as compared to Han (1.6%) in Ningxia (p = 0.004). The frequency of CYP2C19*3/*17 of Hui (1%) was higher as compared to Han (0%) in Ningxia (p = 0.023). The frequencies of alleles (p = 0.142) and genotypes (p = 0.928) were not found to be significantly different among the different BMI groups. The frequencies of four alleles between H. pylori positive and negative groups were not found to be statistically different (p = 0.794). The frequencies of the different genotypes between H. pylori positive and negative groups were not statistically different (p = 0.974), and no statistical difference was observed between the different metabolic phenotypes (p = 0.494). CONCLUSION: There were regional differences observed in CYP2C19*17 distribution in Ningxia. The frequency of CYP2C19*17 in Hui was higher than in Han of Ningxia. No significant relationship was found between CYP2C19 gene polymorphism and susceptibility to H. pylori infection.

Krüppel-Like Factor 2 Is a Gastric Cancer Suppressor and Prognostic Biomarker.

Gastric cancer (GC) is a common digestive tract tumor. Due to its complex pathogenesis, current diagnostic and therapeutic effects remain unsatisfactory. Studies have shown that KLF2, as a tumor suppressor, is downregulated in many human cancers, but its relationship and role with GC remain unclear. In the present study, KLF2 mRNA levels were significantly lower in GC compared to adjacent normal tissues, as analyzed by bioinformatics and RT-qPCR, and correlated with gene mutations. Tissue microarrays combined with immunohistochemical techniques showed downregulation of KLF2 protein expression in GC tissue, which was negatively correlated with patient age, T stage, and overall survival. Further functional experiments showed that knockdown of KLF2 significantly promoted the growth, proliferation, migration, and invasion of HGC-27 and AGS GC cells. In conclusion, low KLF2 expression in GC is associated with poor patient prognosis and contributes to the malignant biological behavior of GC cells. Therefore, KLF2 may serve as a prognostic biomarker and therapeutic target in GC.

Investigation of the Potential Mechanism of Alpinia officinarum Hance in Improving Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.

Objective: We used network pharmacology, molecular docking, and cellular analysis to explore the pharmacodynamic components and action mechanism of Alpinia officinarum Hance (A. officinarum) in improving type 2 diabetes mellitus (T2DM). Methods: The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential targets and mechanism of A. officinarum toward improving T2DM. The first 9 core targets and potential active compounds were docked using Discovery Studio 2019. Finally, IR-HepG2 cells and qPCR were applied to determine the mRNA expression of the top 6 core targets of the PPI network. Results: A total of 29 active ingredients and 607 targets of A. officinarum were obtained. T2DM-related targets overlapped with 176 targets. The core targets of the PPI network were identified as AKT serine/threonine kinase 1 (AKT1), an activator of transcription 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), albumin (ALB), mitogen-activated protein kinase 1 (MAPK1), and peroxisome proliferator-activated receptor gamma (PPARG). A. officinarum performs an antidiabetic role via the AGE-RAGE signaling pathway, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and others, according to GO and KEGG enrichment analyses. Molecular docking revealed that the binding ability of diarylheptanoid active components in A. officinarum to core target protein was higher than that of flavonoids. The cell experiments confirmed that the A. officinarum extracts improved the glucose uptake of IR-HepG2 cells and AKT expression while inhibiting the STAT3, TNF, TP53, SRC, and EGFR mRNA expression. Conclusion: A. officinarum Hance improves T2DM by acting on numerous components, multiple targets, and several pathways. Our results lay the groundwork for the subsequent research and broaden the clinical application of A. officinarum Hance.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

New target DDR1: A "double-edged sword" in solid tumors.

Globally, cancer is a major catastrophic disease that seriously threatens human health. Thus, there is an urgent need to find new strategies to treat cancer. Among them, identifying new targets is one of the best ways to treat cancer at present. Especially in recent years, scientists have discovered many new targets and made breakthroughs in the treatment of cancer, bringing new hope to cancer patients. As one of the novel targets for cancer treatment, DDR1 has attracted much attention due to its unique role in cancer. Hence, here, we focus on a new target, DDR1, which may be a "double-edged sword" of human solid tumors. In this review, we provide a comprehensive overview of how DDR1 acts as a "double-edged sword" in cancer. First, we briefly introduce the structure and normal physiological function of DDR1; Second, we delineate the DDR1 expression pattern in single cells; Next, we sorte out the relationship between DDR1 and cancer, including the abnormal expression of DDR1 in cancer, the mechanism of DDR1 and cancer occurrence, and the value of DDR1 on cancer prognosis. In addition, we introduced the current status of global drug and antibody research and development targeting DDR1 and its future design prospects; Finally, we summarize and look forward to designing more DDR1-targeting drugs in the future to make further progress in the treatment of solid tumors.